ic12 depression Flashcards
Diagnostic criteria of Depression
At least 5 symptoms for 2 weeks and change from previous functioning + Must have either Depressed mood or Loss of interest
In SAD CAGES
Interest (Anhedonia)
Sleep: Insomnia
Appetite: poor, leading to weight loss
Depressed mood / Irritable mood in children
Concentration, decision making
Activity: psychomotor retardation
Guilt: worthlessness
Energy: low
Suicidal thoughts
What should be ruled out for diagnosis of Depression? (2 points)
1) Bipolar disorder, as antidepressants can cause mania
2) Check labs eg. blood glucose, FBC, LFT, TFT to rule out other conditions causing depressive symptoms
Eg. Delirium, psychosis, thyroid dysfunction, diabetes
What are 2 rating scales to assess progress / severity of depression?
Which scale proves remission, which scale proves need to treat?
1) Hamilton Rating Scale for Depression (HAM-D)
Gold standard
Clinician rated
Remission: HAM-D score 7 or below
2) Patient Health Questionnaire (PHQ-9)
Patient self rated
Score ≥ 10 means moderate, Need antidepressant treatment
Non pharm treatment for depression
Should herbal medication be used for depression?
1) Sleep hygiene
2) Psychotherapy, should be adjunct to meds
3) ECT (Electronic convulsive therapy)
St John’s Wort
Can cause alot of DDI eg. serotonin syndrome
Do not use together with antidepressants
What is considered physical symptoms of depression?
How long does it take to resolve?
Sleep, appetite
1-2 weeks
How long do mood symptoms take to improve?
Why?
at least 6 weeks
Due to gradual downregulation of autoreceptors
What are 3 different drug targets for antidepressants?
1) Specific reuptake transporter
Blocks reuptake transporter, so signal can be sustained
Eg. SSRI, SNRI, TCA, Bupropion
2) MAO
MAO breaks down neurotransmitters
Eg. Moclobamide
3) Pre-synaptic autoreceptors
Signals to synapse to reduce release of neurotransmitters
(-) feedback mechanism
Will downregulate after a few weeks of sustained high neurotransmitters
Eg. Mirtazapine (autoreceptor antagonist)
When are antidepressants indicated?
For moderate severity onwards: PHQ-9 score = 10 onwards
What should be recommended for low energy?
Choose something that increase NE, DA
Bupropion or SSRI (Fluoxetine, Escitalopram)
What should be used for patients with sexual disorders from antidepressants
Mirtazapine
Bupropion
What is recommended for pts unable to sleep
Mirtazapine
What are the first line medications for depression (4 points)
SSRI
SNRI
Mirtazapine
Bupropion
Which antidepressants have the least DDI?
Mirtazapine, Escitalopram, Venlafaxine/Desvenlafaxine (SNRI)
What is the MOA of Mirtazapine
NaSSA = Noradrenergic and Specific Serotoninergic Antidepressant
MOA
Antagonise 5HT2, 5HT3 → so that serotonin will bind to 5HT1A receptors
Antagonise A2 autoreceptor → Increase NE
Side effects of Mirtazapine?
Hence when is Mirtazapine indicated?
Sedation (H1 antagonism)
Weight gain (5HT3 antagonism)
No sexual side effects (due to 5HT2 antagonism)
For patients with
1) Has sexual side effects from serotonergic drugs (SSRI, TCA)
2) Poor appetite
3) Cannot sleep
What are SSRIs? (6 points)
They are generally… (3 points)
Selective Serotonin Reuptake Inhibitors
Fluoxetine
Paroxetine
Fluvoxamine
Escitalopram
Citalopram
Sertraline
Generally not sedating, no anticholinergic SE, no orthostatic hypotension
Which is the most problematic SSRI?
Paroxetine: most anticholinergic, sedating, weight gain, shortest half life (causing withdrawal symptoms), 2D6i
Side effect of Escitalopram / Citalopram
QTc prolongation at high dose in elderly
Which SSRI will cause QTc prolongation in elderly at high doses
Escitalopram, Citalopram
What drug should be given with food to increase bioavailability
Sertraline
SSRI with the most DDI
Fluvoxamine (1A2i and 2C19i)
Sertraline should be…
give with food to increase oral bioavailability
Characteristics of Fluoxetine (2 points)
2D6i, long half life
Side effects of SSRI (4 points)
GI side effects
Sexual side effects
Hyponatremia in elderly (SIADH)
Cause drowsiness, confusion, convulsions
increase risk of bleeding in elderly
What are SNRI
Example of SNRI
Selective Serotonin and Norepinephrine Reuptake Inhibitors
Duloxetine
Venlafaxine
Which antidepressant can be used for peripheral neuropathy?
SNRI, cos similar structure to tramadol
Side effects of SNRI
Increase BP (due to increased Norepinephrine)
MOA of Bupropion
Block reuptake of Norepinephrine and Dopamine
When should Bupropion be given? Why?
Should be given in the morning, as it is very stimulating
Side effects of Bupropion (3 points)
SIP
Seizures
Insomnia
Psychosis
Does not help with eating disorder
Which patients are contraindicated in Bupropion (4 points)
History of seizures,
Patients with psychosis
patients with insomnia
patients with eating disorders
What CYP does Bupropion inhibit
2D6 inhibitor (same as Fluoxetine, Paroxetine)
3 examples of TCA
Amitriptyline
Clomipramine
Imipramine
MOA of TCA
Block reuptake of Norepinephrine, Serotonin
Essentially an SNRI
Why are TCA not first line?
Many SE eg. GI, sexual, anticholinergic, sedation, orthostatic hypotension (antagonise a1 adrenoreceptors), conductance abnormalities (if overdose 1 week supply and taken with alcohol)
What causes improvement in antidepressant mood
What causes sexual and GI side effects?
How to overcome these side effects?
Serotonin binding to 5HT1 receptors, hence blocking all other receptors will increase 5HT1 binding
Sexual: Agonism of 5HT2 receptors (cos 2 ppl..)
Occurs in SSRI, TCA
GI: Agonism of 5HT3 (cos 3 parts of colon)
Occurs in SSRI, TCA
Change to Mirtazapine (blocks both 5HT2 and 5HT3 receptors)
Which antidepressants have the longest half lives (2 points)
Fluoxetine
Vortioxetine (a SMS)
What can be used as adjunct to antidepressants if partial treatment
For depression, adjunct to antidepressants
SGA eg. Aripiprazole, Brexpiprazole, Quetiapine XR
Sleep only:
Benzodiazepines
Z-hypnotics
1st gen Antihistamines
Example of MAOi
What should be observed when switching to or from MAOi
Moclobemide
Washout needed
1 day if stopping Moclobemide → another drug
1 week if stopping another drug → Moclobemide
What causes hyponatremia?
SSRI, caused by SIADH
Most impt counselling point in young adults
younger patients ≤ 24 years old, higher risk of suicide
What drugs can cause serotonin syndrome? (7 points)
Triptans
Sibutramine
Opioids
Linezolid
Ritonavir
MAOi
SSRI, SNRI, TCA
Drug food interaction with antidepressants
Space apart with alcohol for 4-6 hours
What happens if suddenly stop taking antidepressant?
Associated with which Antidepressant?
How to manage?
Antidepressant Discontinuation Syndrome
Symptoms: Flu-like symptoms, Insomnia, tingling sensation, anxiety
Paroxetine (SSRI), Venlafaxine (SNRI)
Not life threatening, discomfort to patients
Resolves 1-2 weeks without treatment
Gradually tapering dose by half tablet every 1-2 weeks
Not necessary if drug has long half life or active metabolites eg. Fluoxetine, Vortioxetine (SMS), Bupropion
Counselling points for antidepressants (4 points)
1) Drug will take a few weeks to work
2) Do not take at the same time as alcohol, space 4-6hrs apart
3) If condition is worsening or feel suicidal (esp for ≤ 24 years old), go to the doctor
4) Possible side effects eg. drowsiness, insomnia, orthostatic hypotension, sexual dysfunction
Which antidepressants have short half lives?
Paroxetine, Venlafaxine (hence will have antidepressant discontinuation syndrome)
What is the course of antidepressant therapy?
When to consider changing medication?
At least 6 months
change if ineffective after 2-4 weeks
What are the 2D6 inhibitors
Fluoxetine
Paroxetine
Bupropion
What if a patient is poor metaboliser of 2D6? Which SSRI to give?
Escitalopram, Sertraline
What if patient is poor metaboliser of 2C19? Which SSRI to give?
(FFP)
Fluoxetine, Fluvoxamine, Paroxetine
Which first line is safe to give for poor metaboliser of 2C19 or 2D6?
Bupropion, Mirtazapine
but note that Bupropion is inhibitor of 2D6
